Background:To address the presence and features of outer retinal tubulation(ORT)found in diabetic macular edema(DME)treated with anti-vascular endothelial growth factor(anti-VEGF)and to differentiate between ORT and c...Background:To address the presence and features of outer retinal tubulation(ORT)found in diabetic macular edema(DME)treated with anti-vascular endothelial growth factor(anti-VEGF)and to differentiate between ORT and cystoid DME,which have different plans of management.Methods:This was a retrospective review of a total of 514 patients investigated with spectral domain optical coherence tomography(OCT)in patients with diabetic macular edema treated with anti-VEGF.ORT was seen in 12 eyes of 11 patients.The morphologic characteristics of ORT and its progress over time were examined using OCT data.The retinal images were obtained by horizontal and vertical scans to analyze the possible presence of ORT and to explore their morphologic features and location in the retinal layers.Results:ORT was seen in DME treated with anti-VEGF.ORT was shown as round or ovoid hyporeflective spaces with hyperreflective borders on the B-scans,measuring 30 to 120μm high and 30 to 1775μm wide.The tubules generally remained stable over time.In a retinal practice specializing in advanced diabetic retinopathy clinic,this ORT was seen in 12 eyes of 11 patients during a 12-month period.ORT presented either after receiving 0.05 mL open-label intravitreal injections of 0.5 mg ranibizumab or 1.25 mg bevacizumab.Conclusion:ORT is found in DME treated with anti-VEGF that may show damage to the outer retina secondary to the severity and chronicity of the DME.ORT may be a result of underlying chronic and severe diabetic macular edema that may occur later possibly secondary to retinal layers rearrangement after several anti-VEGF injections.It is important to differentiate between ORT and cystoids DME.The presence of the ORT entity alone without the presence of DME does not require further anti-VEGF re-injections.展开更多
The F-BAR domain containing proteins PACSINs are cytoplasmic phosphoproteins involved in various mem-brane deformations,such as actin reorganization,vesicle transport and microtubule movement.Our previous study shows ...The F-BAR domain containing proteins PACSINs are cytoplasmic phosphoproteins involved in various mem-brane deformations,such as actin reorganization,vesicle transport and microtubule movement.Our previous study shows that all PACSINs are composed of crescent shaped dimers with two wedge loops,and the wedge loop-mediated lateral interaction between neighboring dimers is important for protein packing and tubulation activity.Here,from the crystal packing of PACSIN 2,we observed a tight tip-to-tip interaction,in addition to the wedge loop-mediated lateral interaction.With this tip-to-tip interaction,the whole packing of PACSIN 2 shows a spiral-like assem-bly with a central hole from the top view.Elimination of this tip-to-tip connection inhibited the tubulation function of PACSIN 2,indicating that tip-to-tip interaction plays an important role in membrane deformation activity.Together with our previous study,we proposed a packing model for the assembly of PACSIN 2 on membrane,where the pro-teins are connected by tip-to-tip and wedge loop-mediated lateral interactions on the surface of membrane to gener-ate various diameter tubules.展开更多
Dear Editor,I would like to congratulate Mamsen et al.i on their extensive and scientifically valuable work.I analyzed their raw data presented in Table 1 of the original article from a different perspective and disco...Dear Editor,I would like to congratulate Mamsen et al.i on their extensive and scientifically valuable work.I analyzed their raw data presented in Table 1 of the original article from a different perspective and discovered an effect not mentioned in the article.My analysis showed that luteinizing hormone(LH)levels are significantly lower in patients at high infertility risk(HIR),whose testes lack A dark(Ad)spermatogonia and display an abnormal ratio of germ cells per crosssectional tubule(G/T).展开更多
Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that pla...Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that plays an important role in a broad range of cellular activities from calcium regulation to protein synthesis and trafficking.In neurons,the ER extends from the soma through the axon to presynaptic terminals,and throughout the dendritic arbor into as many as half of all postsynaptic dendritic spines at any given time(Falahati et al.,2022).展开更多
Objective To evaluate effects of cypermethrin on the testis histology and testosterone, LH and FSH in adult male Sprague-Dawley rats. Methods The intact adult male rats were randomly divided into five groups and were ...Objective To evaluate effects of cypermethrin on the testis histology and testosterone, LH and FSH in adult male Sprague-Dawley rats. Methods The intact adult male rats were randomly divided into five groups and were treated with cypermethrin at doses of 0, 7.5, 15, 30, or 60 mg/kg per day by oral gavage for 15-days. After the treatments, serum was collected for hormone assays. The testes, epididymides, seminal vesicles, and prostates were excised and weighed. The right testis was frozen for daily sperm production and the left one was processed for histopathology. Results Daily sperm production decreased significantly in 30 and 60 mg/（kg.day） groups. Testicular structure abnormalities included atrophic and distorted seminiferous tubules, deformed and disordered arrangement of germ cells, reduced germ cells, Sertoli cells and Leydig cells, vacuolization and multinucleated formations of spermatids in the cypermethrin-treated rats. Vacuolization was found in Sertoli cells and the deformed nucleus was noted in Leydig cells. Serum testosterone reduced significantly in 30 and 60 mg/（kg.day） groups. Serum FSH increased significantly in 60 mg/（kg.day） group. Conclusion Cypermethrin induces impairments of the seminiferous tubules structure and spermatogenesis in the rats. The damages of the male reproductive system may be attributed to the imbalance of circulating testosterone.展开更多
The blood-testis barrier （BTB） is found between adjacent Sertoli cells in the testis where it creates a unique microenvironment for the development and maturation of meiotic and postmeiotic germ cells in seminiferou...The blood-testis barrier （BTB） is found between adjacent Sertoli cells in the testis where it creates a unique microenvironment for the development and maturation of meiotic and postmeiotic germ cells in seminiferous tubes. It is a compound proteinous structure, composed of several types of cell junctions including tight junctions （TJs）, adhesion junctions and gap junctions （GJs）. Some of the junctional proteins function as structural proteins of BTB and some have regulatory roles. The deletion or functional silencing of genes encoding these proteins may disrupt the BTB, which may cause immunological or other damages to meiotic and postmeiotic cells and ultimately lead to spermatogenic arrest and infertility. In this review, we will summarize the findings on the BTB structure and function from genetically-modified mouse models and discuss the future perspectives.展开更多
<abstract>Aim: To observe the acute effect of the organophosphorous insecticide malathion on testicular function in mice. Methods: The effects of a single dose of malathion [240 mg/kg (1/12 LD50)] on plasma acet...<abstract>Aim: To observe the acute effect of the organophosphorous insecticide malathion on testicular function in mice. Methods: The effects of a single dose of malathion [240 mg/kg (1/12 LD50)] on plasma acetylcholinesterase (ACE) activity, spermatozoa (epididymal cauda counts and teratozoospermia), testis and plasma testosterone concentration) were evaluated at day 1,8, 16, 35 and 40 after treatment. Results: The sperm count was decreased significantly 24 h after treatment and teratozoospermia was increased at day 35 and 40. The height of the seminiferous epithelium and the diameter of tubular lumen were decreased at day 8. The percentage of tubular blockade was increased between day 8 and 35. A decrease in testosterone plasma level was observed at day 16 after treatment. Conclusion: Malathion damages male reproduction. The depletion of seminiferous tubules and the increase in teratozoospermia may be a genotoxic damage to the renewing spermatogonia, but the possibility of spermatogenic/ spermiogenic disfunction due to a decrease in the plasma testosterone level can not be ruled out.展开更多
The posterior gut of the Drosophila embryo, consisting of hindgut and Malpighian tubules, provides a simple,well-defined system where it is possible to use a genetic approach to define components essential for epithel...The posterior gut of the Drosophila embryo, consisting of hindgut and Malpighian tubules, provides a simple,well-defined system where it is possible to use a genetic approach to define components essential for epithelial morphogenesis.We review here the advantages of Drosophila as a model genetic organism, the morphogenesis of the epithelial structures of the posterior gut, and what is known about the genetic requirements to form these structures.In overview, primordia are patterned by expression of hierarchies of transcription factors; this leads to localized expression of cell signaling molecules, and finally, to the least understood step: modulation of cell adhesion and cell shape. We describe approaches to identify additional genes that are required for morphogenesis of these simple epithelia, particularly those that might play a structural role by affecting cell adhesion and cell shape.展开更多
Aim: To evaluate the effect of tamoxifen citrate on male reproductive system of rat. Methods: Groups of male rats were gavaged with tamoxifen at doses of 200 mg·kg-1·d-1, 400 mg·kg-1·d-1 or 800 mg&...Aim: To evaluate the effect of tamoxifen citrate on male reproductive system of rat. Methods: Groups of male rats were gavaged with tamoxifen at doses of 200 mg·kg-1·d-1, 400 mg·kg-1·d-1 or 800 mg·kg-1·d-1 in 0.1 mL olive oil for 10 consecutive days. Controls were treated with 0.1 mL olive oil. Rats were anesthetized and killed on d 3, d 15 or d 35 after the last dose. Testes were collected, processed for paraffin embedding, sectioned at 5 μm thickness, stained with H&E and analyzed microscopically. Results: There was a dose-dependent increase in the occurrence of seminiferous tubular distortion with germinal cell sloughing. The highest dose increased the number of multinucleated giant cells on d 3 and d 15. Conclusion: Tamoxifen citrate induces multinucleated giant cells and germinal epithelial sloughing in a dose-dependent manner and these changes are detrimental to male fertility.展开更多
This study aimed to evaluate testicular toxicity induced by hydroxyurea （HU） and the possible counteracting effect of an aqueous extract of Cistanche deserticola （CD）. HU is an antineoplastic drug that has potenti...This study aimed to evaluate testicular toxicity induced by hydroxyurea （HU） and the possible counteracting effect of an aqueous extract of Cistanche deserticola （CD）. HU is an antineoplastic drug that has potential reproductive toxicity, and Herba Cistanche has been used as a tonic for the reproductive system for thousands of years. Sixty mice were randomly divided into five groups. Except mice in normal group, the rest received HU （400 mg kg^-1 body weight） intragastrically. Meanwhile, mice in normal and HU control groups received purified water, and the rest received intragastrically three doses of CD decoctions （1.5, 3.0 and 6.0 g crude drug kg^-1 body weight, respectively） daily for 4 weeks. Severe testes lesions were observed, testes weight （P〈0.01） and serum luteinising hormone levels （P〈0.0 1） were also decreased significantly, in the HU groups. Three doses of CD decoctions alleviated the spermatogenetic cell degeneration induced by HU and modulated the serum sex hormones levels to some extent.展开更多
Aim: To study the contraceptive effect of the crude extracts of Curcuma longa in male albino rats. Methods: Rats were fed orally with Curcuma longa aqueous and 70 % alcoholic extract for 60 days (500 mg·kg-1·...Aim: To study the contraceptive effect of the crude extracts of Curcuma longa in male albino rats. Methods: Rats were fed orally with Curcuma longa aqueous and 70 % alcoholic extract for 60 days (500 mg·kg-1· day-1). Results: A reduction in sperm motility and density was observed in both the treated groups. Conclusion: Curcuma longa may have affected the androgen synthesis either by inhibiting the Leydig cell function or the hypo-thalamus pituitary axis and as a result, spermatogenesis is arrested.展开更多
To verify the theoretical models of varying transversely isotropic stress-strain relations of dentin established in the preceding work(Part Ⅰ),we per- form a set of experiments.Because of the very fine tooth size,it ...To verify the theoretical models of varying transversely isotropic stress-strain relations of dentin established in the preceding work(Part Ⅰ),we per- form a set of experiments.Because of the very fine tooth size,it usually seems to be difficult to directly measure the inhomogeneous and anisotropic parameters of dentin.In this paper,by the digital speckle correlation method,tensile experiments are made on the small dentin samples either parallel or perpendicular to the dentin tubules.With the theoretically predicted elastic stress-strain relations,an optimiza- tion method is proposed to fit the strain curve adapted to the experimental data. The results show that the theoretical elastic stress-strain relations coincides very well with the experimental observations.The determined Young's modulus and Poisson's ratio of dentin matrix are 29.5GPa and 0.44,respectively,in the optimization sense.展开更多
Background:Female sperm storage(FSS),the maintenance of sperm inside the female reproductive tract for an extended period of time,is pervasive among organisms with internal fertilization.Because FSS enables asynchrono...Background:Female sperm storage(FSS),the maintenance of sperm inside the female reproductive tract for an extended period of time,is pervasive among organisms with internal fertilization.Because FSS enables asynchronous mating and fertilization,it could be extremely important to reproduction.However,the physiological mechanisms underlying prolonged preservation and maintenance are poorly understood.Here,we used chicken,a typical oviparous animal,to determine the mechanisms ensuring sperm functionality in sperm storage tubules(SSTs).Results:We performed an insemination experiment on over two thousand hens at two periods,and found that the FSS capabilities varied widely among individuals.Except for the differences in the SST density between the two groups with distinct FSS abilities,we quantitatively profiled small-molecule metabolites derived from SST cells,and identified 28 metabolites with differential expression.In particular,high levels of lipids,fatty acids and lipid peroxidation product were observed in hens with low FSS capability.Pathway analysis showed that these differential metabolites were significantly enriched in the biosynthesis of unsaturated fatty acids.Moreover,we detected the total antioxidant capacity and lipid peroxidation level of SSTs,and found that chickens with a lower FSS ability had a significantly higher content of lipid peroxidation end-product,which was 2.4-fold greater than chickens with a higher FSS capability,and no significant difference was found in the total antioxidant capacity between these two groups.Conclusions:Our findings reveal that the long-term storage of sperm and the maintenance of their function in the female reproductive tract require an adequate microenvironment.The superabundance of fatty acids secreted by SST cells had detrimental effects on sperm storage in the female reproductive tract.Lipid peroxidation produces toxic biological substances that may cause irreversible damage to resident spermatozoa,resulting in short-term sperm retention and decreased fertility.Our findings provide new avenues for studying sperm storage and sustaining fertility.展开更多
Carbon monoxide（CO）,as a vital small molecule in signaling pathways,is found to be involved in ischemia-reperfusion injury（IRI） in renal transplantation.CO-releasing molecule-2（CORM-2）,a CO-releasing molecule,is...Carbon monoxide（CO）,as a vital small molecule in signaling pathways,is found to be involved in ischemia-reperfusion injury（IRI） in renal transplantation.CO-releasing molecule-2（CORM-2）,a CO-releasing molecule,is a type of metal carbonyl complexes which can quickly release CO in vivo.In this study,an in vitro oxidative stress injury model was established to examine the effect of CORM-2 pretreatment on the nuclear-cytoplasmic translocation of high mobility group box 1 protein（HMGB1） in mouse primary renal proximal tubular epithelial cells（RPTECs）.Immunofluorescence staining showed that HMGB1 in the medium-and CORM-2-treated groups was predominantly localized in the nucleus of the cells,whereas higher amounts of HMGB1 translocated to the cytoplasm in the H2O2-and inactive CORM-2（i CORM-2）-treated groups.Western blotting of HMGB1 showed that the total amounts of cytoplasmic HMGB1 in the H2O2-treated（0.59±0.27） and i CORM-2-treated（0.57±0.22） groups were markedly higher than those in the medium-treated（0.19±0.05） and CORM-2-treated（0.21±0.10） groups（P〈0.05）.Co-immunoprecipitation showed that the levels of acetylated HMGB1 in the H2O2-treated（642.98±57.25） and i CORM-2-treated（342.11±131.25） groups were markedly increased as compared with the medium-treated（78.72±74.17） and CORM-2-treated（71.42±53.35） groups（P〈0.05）,and no significant difference was observed between the medium-treated and CORM-2-treated groups（P〉0.05）.In conclusion,our study demonstrated that in the in vitro oxidative stress injury model of primary RPTECs,CORM-2 can significantly inhibit the nuclear-cytoplasmic translocation of HMGB1,which is probably associated with the prevention of HMGB1 acetylation.展开更多
Nerve regeneration after delayed nerve repair is often unsuccessful. Indeed, the expression of genes associated with regeneration, including neurotrophic and gliotrophic factors, is drastically reduced in the distal s...Nerve regeneration after delayed nerve repair is often unsuccessful. Indeed, the expression of genes associated with regeneration, including neurotrophic and gliotrophic factors, is drastically reduced in the distal stump of chronically transected nerves; moreover, Schwann cells undergo atrophy, losing their ability to sustain regeneration. In the present study, to provide a three-dimensional environment and trophic factors supporting Schwann cell activity and axon re-growth, we combined the use of an effective conduit(a chitosan tube) with a promising intraluminal structure(fresh longitudinal skeletal muscle fibers). This enriched conduit was used to repair a 10-mm rat median nerve gap after 3-month delay and functional and morphometrical analyses were performed 4 months after nerve reconstruction. Our data show that the enriched chitosan conduit is as effective as the hollow chitosan conduit in promoting nerve regeneration,and its efficacy is not statistically different from the autograft, considered the "gold standard" technique for nerve reconstruction. Since hollow tubes not always lead to good results after long defects(> 20 mm), we believe that the conduit enriched with fresh muscle fibers could be a promising strategy to repair longer gaps, as muscle fibers create a favorable three-dimensional environment and release trophic factors. All procedures were approved by the Bioethical Committee of the University of Torino and by the Italian Ministry of Health(approval number: 864/2016/PR) on September 14, 2016.展开更多
Aim: To study the effect of ligustrum fruit on spermatogenesis and blood gonadal hormones in diabetic rats.Methods: Experimental diabetes was induced in male Wistar rats with streptozotocin. Ligustrum fruit extract wa...Aim: To study the effect of ligustrum fruit on spermatogenesis and blood gonadal hormones in diabetic rats.Methods: Experimental diabetes was induced in male Wistar rats with streptozotocin. Ligustrum fruit extract wasgiven by gastric gavage at a dose of crude drug 30 g·kg^(-1)·d^(-1) for 110 days. The serum gonadadotropic hormones andtestosterone were determined on d 60 and testicular histology examined on d 110. Results: In the control diabeticrats, the seminiferous tubules were dilated and the spermatogenic cells irregularly arranged. Spermatogenesis was arrest-ed with the number of spermatids highly reduced and spermatozoa not observed. In the treated rats, all types of sper-matogenic cells were practically normal. The serum luteinizing hormone (LH), follicle-stimulating hormone (FSH)and testosterone levels were higher in the treated than in the control rats, but the difference was insignificant. Conclu-sion: In experimental diabetic rats, ligustrum fruit extract protects the damaging effect of experimental diabetes onspermatogenesis. (Asian J Androl 2001 Mar; 3 : 71-73)展开更多
As known, there is a large number of dentin tubules in dentin. These tubules have varying radii and are shaped into radially parallel pattern. The anisotropy of microstructure of dentin shows that dentin should be tre...As known, there is a large number of dentin tubules in dentin. These tubules have varying radii and are shaped into radially parallel pattern. The anisotropy of microstructure of dentin shows that dentin should be treated as a ma- terial of varying transverse isotropy. In this Part, the elastic stress-strain relations and the quadratic strength criterion are established in the form of having varying transverse isotropy, in the framework of micromechanics to take into account of the effect of the microstructures-dentin tubules. Simplified forms for isotropic and ho- mogeneous cases, as well as the corresponding plane stress form of the stress-strain relations are also given. These theoretical models are very well supported by the experiments shown later in the continued paper (Part Ⅱ).展开更多
The authors reviewed the results of their research on the structure and composition of normal and varicocele semi-niferous tubules in adolescents. They give new evidences of normal structure of adolescent testis and d...The authors reviewed the results of their research on the structure and composition of normal and varicocele semi-niferous tubules in adolescents. They give new evidences of normal structure of adolescent testis and demonstrate, forthe first time, the ultrastructural and immunohistochemical modifications of the lamina propria and basal lamina in theadolescent varicocele patients, which are similar to those observed in adults, but less severe, and of the adherence junc-tions in seminiferous tubules. They also report the presence of oxidative stress in adolescents limited to testis and notgeneralised as in the adults. These data are well correlated to different clinical studies that support the hypothesis of aprogressive course of varicocele and the need for surgical treatment in adolescent varicocele patients. (Asian J Androl2001 Dec; 3: 259-262)展开更多
Aim: To evaluate the effect of acute lead chloride exposure on testis and sperm parameters in mice. Methods: PbCl2, 74 mg/kg, was daily administered to sexually mature male mice for 3 days and the effects on the testi...Aim: To evaluate the effect of acute lead chloride exposure on testis and sperm parameters in mice. Methods: PbCl2, 74 mg/kg, was daily administered to sexually mature male mice for 3 days and the effects on the testicular histology and ultrastructure as well as the motility and density of spermatozoa in cauda epididymis were observed. An additional group of mice were treated for 1-3 days and were allowed to recover for 32 days to determine the reversibility of lead-induced changes. Results: The testicular weight, seminiferous tubular diameter and sperm counts were significantly decreased following 3 days of PbCl2 treatment, but were unaffected by shorter-term exposures. The changes caused by lead are mostly reversible. Conclusion: Acute lead chloride exposure injures the fertility parameters of male mice and the effects are partially reversible.展开更多
Mice deficient in the transcription factor pleomorphic adenoma gene 1(PLAG1)exhibit reproductive issues that are characterized,in part,by decreased progressive sperm motility in the male.However,the underlying cause o...Mice deficient in the transcription factor pleomorphic adenoma gene 1(PLAG1)exhibit reproductive issues that are characterized,in part,by decreased progressive sperm motility in the male.However,the underlying cause of this impairment is unknown.As epididymal transit is critical for sperm maturation and motility,the morphology of the epididymis of Plag1-deficient mice was investigated and the spatial expression patterns of PLAG1 protein and mRNA were identified.Using X-gal staining and in situ hybridization,PLAG1 was shown to be widely expressed in both the epithelium and stroma in all regions of the mouse epididymis.Interestingly,the X-gal staining pattern was markedly different in the cauda,where it could be suggestive of PLAG1 secretion into the epididymal lumen.At all ages investigated,the morphology of epididymides from Plag1 knockout(KO)mice was aberrant;the tubule failed to elongate and coil,particularly in the corpus and cauda,and the cauda was malformed,lacking its usual bulbous shape.Moreover,the epididymides from Plag1 KO mice were significantly reduced in size relative to body weight.In 20%of Plag1-deficient mice,the left testicle and epididymis were lacking.The impaired morphogenesis of the epididymal tubule is likely to be a major contributing factor to the fertility problems observed in male Plag1-deficient mice.These results also establish PLAG1 as an important regulator of male reproduction,not only through its involvement in testicular sperm production,but also via its role in the development and function of the epididymis.展开更多
文摘Background:To address the presence and features of outer retinal tubulation(ORT)found in diabetic macular edema(DME)treated with anti-vascular endothelial growth factor(anti-VEGF)and to differentiate between ORT and cystoid DME,which have different plans of management.Methods:This was a retrospective review of a total of 514 patients investigated with spectral domain optical coherence tomography(OCT)in patients with diabetic macular edema treated with anti-VEGF.ORT was seen in 12 eyes of 11 patients.The morphologic characteristics of ORT and its progress over time were examined using OCT data.The retinal images were obtained by horizontal and vertical scans to analyze the possible presence of ORT and to explore their morphologic features and location in the retinal layers.Results:ORT was seen in DME treated with anti-VEGF.ORT was shown as round or ovoid hyporeflective spaces with hyperreflective borders on the B-scans,measuring 30 to 120μm high and 30 to 1775μm wide.The tubules generally remained stable over time.In a retinal practice specializing in advanced diabetic retinopathy clinic,this ORT was seen in 12 eyes of 11 patients during a 12-month period.ORT presented either after receiving 0.05 mL open-label intravitreal injections of 0.5 mg ranibizumab or 1.25 mg bevacizumab.Conclusion:ORT is found in DME treated with anti-VEGF that may show damage to the outer retina secondary to the severity and chronicity of the DME.ORT may be a result of underlying chronic and severe diabetic macular edema that may occur later possibly secondary to retinal layers rearrangement after several anti-VEGF injections.It is important to differentiate between ORT and cystoids DME.The presence of the ORT entity alone without the presence of DME does not require further anti-VEGF re-injections.
基金the National High Technology and Develop-ment Program of China(973 Programs)(No.2010CB911800)the National Natural Science Foundation of China(Grant No.30930020).
文摘The F-BAR domain containing proteins PACSINs are cytoplasmic phosphoproteins involved in various mem-brane deformations,such as actin reorganization,vesicle transport and microtubule movement.Our previous study shows that all PACSINs are composed of crescent shaped dimers with two wedge loops,and the wedge loop-mediated lateral interaction between neighboring dimers is important for protein packing and tubulation activity.Here,from the crystal packing of PACSIN 2,we observed a tight tip-to-tip interaction,in addition to the wedge loop-mediated lateral interaction.With this tip-to-tip interaction,the whole packing of PACSIN 2 shows a spiral-like assem-bly with a central hole from the top view.Elimination of this tip-to-tip connection inhibited the tubulation function of PACSIN 2,indicating that tip-to-tip interaction plays an important role in membrane deformation activity.Together with our previous study,we proposed a packing model for the assembly of PACSIN 2 on membrane,where the pro-teins are connected by tip-to-tip and wedge loop-mediated lateral interactions on the surface of membrane to gener-ate various diameter tubules.
文摘Dear Editor,I would like to congratulate Mamsen et al.i on their extensive and scientifically valuable work.I analyzed their raw data presented in Table 1 of the original article from a different perspective and discovered an effect not mentioned in the article.My analysis showed that luteinizing hormone(LH)levels are significantly lower in patients at high infertility risk(HIR),whose testes lack A dark(Ad)spermatogonia and display an abnormal ratio of germ cells per crosssectional tubule(G/T).
基金supported by AHA Career Development Award 938683 (to PJD)NIH grant R01MH123700 (to MLD)
文摘Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that plays an important role in a broad range of cellular activities from calcium regulation to protein synthesis and trafficking.In neurons,the ER extends from the soma through the axon to presynaptic terminals,and throughout the dendritic arbor into as many as half of all postsynaptic dendritic spines at any given time(Falahati et al.,2022).
基金supported by National Natural Science Foundation of China (NSFC,No.30872143)the Project was funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)Foundation of XuZhou Medical College (2010KJ26)
文摘Objective To evaluate effects of cypermethrin on the testis histology and testosterone, LH and FSH in adult male Sprague-Dawley rats. Methods The intact adult male rats were randomly divided into five groups and were treated with cypermethrin at doses of 0, 7.5, 15, 30, or 60 mg/kg per day by oral gavage for 15-days. After the treatments, serum was collected for hormone assays. The testes, epididymides, seminal vesicles, and prostates were excised and weighed. The right testis was frozen for daily sperm production and the left one was processed for histopathology. Results Daily sperm production decreased significantly in 30 and 60 mg/（kg.day） groups. Testicular structure abnormalities included atrophic and distorted seminiferous tubules, deformed and disordered arrangement of germ cells, reduced germ cells, Sertoli cells and Leydig cells, vacuolization and multinucleated formations of spermatids in the cypermethrin-treated rats. Vacuolization was found in Sertoli cells and the deformed nucleus was noted in Leydig cells. Serum testosterone reduced significantly in 30 and 60 mg/（kg.day） groups. Serum FSH increased significantly in 60 mg/（kg.day） group. Conclusion Cypermethrin induces impairments of the seminiferous tubules structure and spermatogenesis in the rats. The damages of the male reproductive system may be attributed to the imbalance of circulating testosterone.
基金This work was supported by the National Basic Research Program （Nos. 2013CB947900, 2013CB945502 and 2014CB943101） of China （973）, by grants from National Natural Science Foundation of China （No. 31371519） and the Knowledge Innovation Program of the Chinese Academy of Sciences （No. KSCX2-EW-R-07）.
文摘The blood-testis barrier （BTB） is found between adjacent Sertoli cells in the testis where it creates a unique microenvironment for the development and maturation of meiotic and postmeiotic germ cells in seminiferous tubes. It is a compound proteinous structure, composed of several types of cell junctions including tight junctions （TJs）, adhesion junctions and gap junctions （GJs）. Some of the junctional proteins function as structural proteins of BTB and some have regulatory roles. The deletion or functional silencing of genes encoding these proteins may disrupt the BTB, which may cause immunological or other damages to meiotic and postmeiotic cells and ultimately lead to spermatogenic arrest and infertility. In this review, we will summarize the findings on the BTB structure and function from genetically-modified mouse models and discuss the future perspectives.
文摘<abstract>Aim: To observe the acute effect of the organophosphorous insecticide malathion on testicular function in mice. Methods: The effects of a single dose of malathion [240 mg/kg (1/12 LD50)] on plasma acetylcholinesterase (ACE) activity, spermatozoa (epididymal cauda counts and teratozoospermia), testis and plasma testosterone concentration) were evaluated at day 1,8, 16, 35 and 40 after treatment. Results: The sperm count was decreased significantly 24 h after treatment and teratozoospermia was increased at day 35 and 40. The height of the seminiferous epithelium and the diameter of tubular lumen were decreased at day 8. The percentage of tubular blockade was increased between day 8 and 35. A decrease in testosterone plasma level was observed at day 16 after treatment. Conclusion: Malathion damages male reproduction. The depletion of seminiferous tubules and the increase in teratozoospermia may be a genotoxic damage to the renewing spermatogonia, but the possibility of spermatogenic/ spermiogenic disfunction due to a decrease in the plasma testosterone level can not be ruled out.
文摘The posterior gut of the Drosophila embryo, consisting of hindgut and Malpighian tubules, provides a simple,well-defined system where it is possible to use a genetic approach to define components essential for epithelial morphogenesis.We review here the advantages of Drosophila as a model genetic organism, the morphogenesis of the epithelial structures of the posterior gut, and what is known about the genetic requirements to form these structures.In overview, primordia are patterned by expression of hierarchies of transcription factors; this leads to localized expression of cell signaling molecules, and finally, to the least understood step: modulation of cell adhesion and cell shape. We describe approaches to identify additional genes that are required for morphogenesis of these simple epithelia, particularly those that might play a structural role by affecting cell adhesion and cell shape.
文摘Aim: To evaluate the effect of tamoxifen citrate on male reproductive system of rat. Methods: Groups of male rats were gavaged with tamoxifen at doses of 200 mg·kg-1·d-1, 400 mg·kg-1·d-1 or 800 mg·kg-1·d-1 in 0.1 mL olive oil for 10 consecutive days. Controls were treated with 0.1 mL olive oil. Rats were anesthetized and killed on d 3, d 15 or d 35 after the last dose. Testes were collected, processed for paraffin embedding, sectioned at 5 μm thickness, stained with H&E and analyzed microscopically. Results: There was a dose-dependent increase in the occurrence of seminiferous tubular distortion with germinal cell sloughing. The highest dose increased the number of multinucleated giant cells on d 3 and d 15. Conclusion: Tamoxifen citrate induces multinucleated giant cells and germinal epithelial sloughing in a dose-dependent manner and these changes are detrimental to male fertility.
文摘This study aimed to evaluate testicular toxicity induced by hydroxyurea （HU） and the possible counteracting effect of an aqueous extract of Cistanche deserticola （CD）. HU is an antineoplastic drug that has potential reproductive toxicity, and Herba Cistanche has been used as a tonic for the reproductive system for thousands of years. Sixty mice were randomly divided into five groups. Except mice in normal group, the rest received HU （400 mg kg^-1 body weight） intragastrically. Meanwhile, mice in normal and HU control groups received purified water, and the rest received intragastrically three doses of CD decoctions （1.5, 3.0 and 6.0 g crude drug kg^-1 body weight, respectively） daily for 4 weeks. Severe testes lesions were observed, testes weight （P〈0.01） and serum luteinising hormone levels （P〈0.0 1） were also decreased significantly, in the HU groups. Three doses of CD decoctions alleviated the spermatogenetic cell degeneration induced by HU and modulated the serum sex hormones levels to some extent.
文摘Aim: To study the contraceptive effect of the crude extracts of Curcuma longa in male albino rats. Methods: Rats were fed orally with Curcuma longa aqueous and 70 % alcoholic extract for 60 days (500 mg·kg-1· day-1). Results: A reduction in sperm motility and density was observed in both the treated groups. Conclusion: Curcuma longa may have affected the androgen synthesis either by inhibiting the Leydig cell function or the hypo-thalamus pituitary axis and as a result, spermatogenesis is arrested.
基金The project supported by the National Natural Science Foundation of China(19525207)
文摘To verify the theoretical models of varying transversely isotropic stress-strain relations of dentin established in the preceding work(Part Ⅰ),we per- form a set of experiments.Because of the very fine tooth size,it usually seems to be difficult to directly measure the inhomogeneous and anisotropic parameters of dentin.In this paper,by the digital speckle correlation method,tensile experiments are made on the small dentin samples either parallel or perpendicular to the dentin tubules.With the theoretically predicted elastic stress-strain relations,an optimiza- tion method is proposed to fit the strain curve adapted to the experimental data. The results show that the theoretical elastic stress-strain relations coincides very well with the experimental observations.The determined Young's modulus and Poisson's ratio of dentin matrix are 29.5GPa and 0.44,respectively,in the optimization sense.
基金This work was supported by Programs for Changjiang Scholars and Innovative Research in Universities(IRT_15R62)China Agriculture Research Systems(No.CARS_40).
文摘Background:Female sperm storage(FSS),the maintenance of sperm inside the female reproductive tract for an extended period of time,is pervasive among organisms with internal fertilization.Because FSS enables asynchronous mating and fertilization,it could be extremely important to reproduction.However,the physiological mechanisms underlying prolonged preservation and maintenance are poorly understood.Here,we used chicken,a typical oviparous animal,to determine the mechanisms ensuring sperm functionality in sperm storage tubules(SSTs).Results:We performed an insemination experiment on over two thousand hens at two periods,and found that the FSS capabilities varied widely among individuals.Except for the differences in the SST density between the two groups with distinct FSS abilities,we quantitatively profiled small-molecule metabolites derived from SST cells,and identified 28 metabolites with differential expression.In particular,high levels of lipids,fatty acids and lipid peroxidation product were observed in hens with low FSS capability.Pathway analysis showed that these differential metabolites were significantly enriched in the biosynthesis of unsaturated fatty acids.Moreover,we detected the total antioxidant capacity and lipid peroxidation level of SSTs,and found that chickens with a lower FSS ability had a significantly higher content of lipid peroxidation end-product,which was 2.4-fold greater than chickens with a higher FSS capability,and no significant difference was found in the total antioxidant capacity between these two groups.Conclusions:Our findings reveal that the long-term storage of sperm and the maintenance of their function in the female reproductive tract require an adequate microenvironment.The superabundance of fatty acids secreted by SST cells had detrimental effects on sperm storage in the female reproductive tract.Lipid peroxidation produces toxic biological substances that may cause irreversible damage to resident spermatozoa,resulting in short-term sperm retention and decreased fertility.Our findings provide new avenues for studying sperm storage and sustaining fertility.
基金supported by the National Natural Science Foundation of China(No.81300574)
文摘Carbon monoxide（CO）,as a vital small molecule in signaling pathways,is found to be involved in ischemia-reperfusion injury（IRI） in renal transplantation.CO-releasing molecule-2（CORM-2）,a CO-releasing molecule,is a type of metal carbonyl complexes which can quickly release CO in vivo.In this study,an in vitro oxidative stress injury model was established to examine the effect of CORM-2 pretreatment on the nuclear-cytoplasmic translocation of high mobility group box 1 protein（HMGB1） in mouse primary renal proximal tubular epithelial cells（RPTECs）.Immunofluorescence staining showed that HMGB1 in the medium-and CORM-2-treated groups was predominantly localized in the nucleus of the cells,whereas higher amounts of HMGB1 translocated to the cytoplasm in the H2O2-and inactive CORM-2（i CORM-2）-treated groups.Western blotting of HMGB1 showed that the total amounts of cytoplasmic HMGB1 in the H2O2-treated（0.59±0.27） and i CORM-2-treated（0.57±0.22） groups were markedly higher than those in the medium-treated（0.19±0.05） and CORM-2-treated（0.21±0.10） groups（P〈0.05）.Co-immunoprecipitation showed that the levels of acetylated HMGB1 in the H2O2-treated（642.98±57.25） and i CORM-2-treated（342.11±131.25） groups were markedly increased as compared with the medium-treated（78.72±74.17） and CORM-2-treated（71.42±53.35） groups（P〈0.05）,and no significant difference was observed between the medium-treated and CORM-2-treated groups（P〉0.05）.In conclusion,our study demonstrated that in the in vitro oxidative stress injury model of primary RPTECs,CORM-2 can significantly inhibit the nuclear-cytoplasmic translocation of HMGB1,which is probably associated with the prevention of HMGB1 acetylation.
基金supported by the European Community’s Seventh Framework Programme(FP7-HEALTH-2011),No.278612(to SG)by Compagnia di San Paolo,No.D86D15000100005InTheCure project(to SR)
文摘Nerve regeneration after delayed nerve repair is often unsuccessful. Indeed, the expression of genes associated with regeneration, including neurotrophic and gliotrophic factors, is drastically reduced in the distal stump of chronically transected nerves; moreover, Schwann cells undergo atrophy, losing their ability to sustain regeneration. In the present study, to provide a three-dimensional environment and trophic factors supporting Schwann cell activity and axon re-growth, we combined the use of an effective conduit(a chitosan tube) with a promising intraluminal structure(fresh longitudinal skeletal muscle fibers). This enriched conduit was used to repair a 10-mm rat median nerve gap after 3-month delay and functional and morphometrical analyses were performed 4 months after nerve reconstruction. Our data show that the enriched chitosan conduit is as effective as the hollow chitosan conduit in promoting nerve regeneration,and its efficacy is not statistically different from the autograft, considered the "gold standard" technique for nerve reconstruction. Since hollow tubes not always lead to good results after long defects(> 20 mm), we believe that the conduit enriched with fresh muscle fibers could be a promising strategy to repair longer gaps, as muscle fibers create a favorable three-dimensional environment and release trophic factors. All procedures were approved by the Bioethical Committee of the University of Torino and by the Italian Ministry of Health(approval number: 864/2016/PR) on September 14, 2016.
文摘Aim: To study the effect of ligustrum fruit on spermatogenesis and blood gonadal hormones in diabetic rats.Methods: Experimental diabetes was induced in male Wistar rats with streptozotocin. Ligustrum fruit extract wasgiven by gastric gavage at a dose of crude drug 30 g·kg^(-1)·d^(-1) for 110 days. The serum gonadadotropic hormones andtestosterone were determined on d 60 and testicular histology examined on d 110. Results: In the control diabeticrats, the seminiferous tubules were dilated and the spermatogenic cells irregularly arranged. Spermatogenesis was arrest-ed with the number of spermatids highly reduced and spermatozoa not observed. In the treated rats, all types of sper-matogenic cells were practically normal. The serum luteinizing hormone (LH), follicle-stimulating hormone (FSH)and testosterone levels were higher in the treated than in the control rats, but the difference was insignificant. Conclu-sion: In experimental diabetic rats, ligustrum fruit extract protects the damaging effect of experimental diabetes onspermatogenesis. (Asian J Androl 2001 Mar; 3 : 71-73)
基金The project supported by the National Natural Science Foundation of China (19525207).
文摘As known, there is a large number of dentin tubules in dentin. These tubules have varying radii and are shaped into radially parallel pattern. The anisotropy of microstructure of dentin shows that dentin should be treated as a ma- terial of varying transverse isotropy. In this Part, the elastic stress-strain relations and the quadratic strength criterion are established in the form of having varying transverse isotropy, in the framework of micromechanics to take into account of the effect of the microstructures-dentin tubules. Simplified forms for isotropic and ho- mogeneous cases, as well as the corresponding plane stress form of the stress-strain relations are also given. These theoretical models are very well supported by the experiments shown later in the continued paper (Part Ⅱ).
文摘The authors reviewed the results of their research on the structure and composition of normal and varicocele semi-niferous tubules in adolescents. They give new evidences of normal structure of adolescent testis and demonstrate, forthe first time, the ultrastructural and immunohistochemical modifications of the lamina propria and basal lamina in theadolescent varicocele patients, which are similar to those observed in adults, but less severe, and of the adherence junc-tions in seminiferous tubules. They also report the presence of oxidative stress in adolescents limited to testis and notgeneralised as in the adults. These data are well correlated to different clinical studies that support the hypothesis of aprogressive course of varicocele and the need for surgical treatment in adolescent varicocele patients. (Asian J Androl2001 Dec; 3: 259-262)
文摘Aim: To evaluate the effect of acute lead chloride exposure on testis and sperm parameters in mice. Methods: PbCl2, 74 mg/kg, was daily administered to sexually mature male mice for 3 days and the effects on the testicular histology and ultrastructure as well as the motility and density of spermatozoa in cauda epididymis were observed. An additional group of mice were treated for 1-3 days and were allowed to recover for 32 days to determine the reversibility of lead-induced changes. Results: The testicular weight, seminiferous tubular diameter and sperm counts were significantly decreased following 3 days of PbCl2 treatment, but were unaffected by shorter-term exposures. The changes caused by lead are mostly reversible. Conclusion: Acute lead chloride exposure injures the fertility parameters of male mice and the effects are partially reversible.
文摘Mice deficient in the transcription factor pleomorphic adenoma gene 1(PLAG1)exhibit reproductive issues that are characterized,in part,by decreased progressive sperm motility in the male.However,the underlying cause of this impairment is unknown.As epididymal transit is critical for sperm maturation and motility,the morphology of the epididymis of Plag1-deficient mice was investigated and the spatial expression patterns of PLAG1 protein and mRNA were identified.Using X-gal staining and in situ hybridization,PLAG1 was shown to be widely expressed in both the epithelium and stroma in all regions of the mouse epididymis.Interestingly,the X-gal staining pattern was markedly different in the cauda,where it could be suggestive of PLAG1 secretion into the epididymal lumen.At all ages investigated,the morphology of epididymides from Plag1 knockout(KO)mice was aberrant;the tubule failed to elongate and coil,particularly in the corpus and cauda,and the cauda was malformed,lacking its usual bulbous shape.Moreover,the epididymides from Plag1 KO mice were significantly reduced in size relative to body weight.In 20%of Plag1-deficient mice,the left testicle and epididymis were lacking.The impaired morphogenesis of the epididymal tubule is likely to be a major contributing factor to the fertility problems observed in male Plag1-deficient mice.These results also establish PLAG1 as an important regulator of male reproduction,not only through its involvement in testicular sperm production,but also via its role in the development and function of the epididymis.
